Congenital 6-phosphogluconate dehydrogenase (6PGD) deficiency associated with chronic hemolytic anemia in a Spanish family

✍ Scribed by Corrons, J. Ll. Vives; Colomer, D.; Pujades, A.; Rovira, A.; Aymerich, M.; Merino, A.; Bascompte, J. Ll. Aguilar i

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 615 KB
• Volume: 53
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199612)53:4<221::aid-ajh2>3.0.co;2-#

✦ Synopsis

Clinical and metabolic studies were performed in four members of a Spanish family with partial (50%) 6 phosphogluconate dehydrogenase (6PGD) deficiency. In all cases the activities of 6 phosphogluconolactone (6PGL) and glutathione reductase (GR) were normal, and the molecular characterization performed in the partially purified 6PGD from the propositus showed normal kinetic and electrophoretic patterns. Two females (the propositus and her sister) suffered from a well-compensated chronic nonspherocytic hemolytic anemia (CNSHA) and exhibited decreased RBC glutathione (GSH) stability with increased oxidative susceptibility, defined by enhanced malonyldialdehyde (MDA) generation "in vitro." The other two members of the family (the propositus's mother and brother) were clinically asymptomatic. In the propositus and her sister, RBC metabolism exhibited a markedly abnormal concentration of glycolytic intermediates, mainly characterized by striking increases in fructose 1,6 bisphosphate (50-fold), dihydroxiacetone-phosphate (20-fold) and glyceraldehyde 3-phosphate (tenfold). Although the precise mechanism of the hemolysis in the two patients is unknown, the enhanced oxidative threat observed in their RBCs may interfere in some way with the glycolytic pathway function, leading to a marked increase in certain metabolic intermediates located before the glyceraldehyde 3 phosphate dehydrogenase (GA3PD) step. Since it seems that GA3PD half-life is modulated by fluctuations of the cytosolic redox status, an "in situ" approach was simulated by using permeabilized RBCs. In these conditions, GA3PD activity was significantly lower in the propositus and her sister than in the asymptomatic members of the family and the simultaneous normal control.